Ribo- and deoxyribonucleoside 5'-mono-, di-, and triphosphates play key roles in the metabolism of nucleic acids. Analogues in which a non- bridging oxygen is replaced with another group can serve to not only provide fundamental information on the mechanism of important enzymatic reactions, but control such reactions for medical and pharmacological purposes. In Phase I, synthetic routes were successfully developed to prepare nucleoside phosphate analogues in which a borane group was attached to phosphorus. Replacement of a non-bridging oxygen with an isoelectronic BH3 gives a similarly charged moiety (P-O--->PBH3-) but one which cannot coordinate to metal ions nor hydrogen bond and is more lipophilic. Thymidine and adenosine-5'-borano-monophosphate and a thymidine-5'-alpha-boranotriphosphate were prepared. The boronated thymidine triphosphate was found to substitute for the normal dTTP in a DNA polymerase experiment. Thymidine 5'-boranophosphate is a substrate of acid phosphatase unlike thymidine 5'-thiophosphate, indicating complementary uses to probe details of enzymic reactions. Cytotoxicity in tumor screens has been found. The proposed Phase II effort involves the preparation of a variety of nucleoside 5'-mono-, di-, and triphosphates with borane substitution on phosphorus. Modified boronated nucleotides with greater lipophilicity will be prepared to produce enhanced concentrations of the free boronated nucleotide inside cells for pharmacological potency. Extensive enzymatic studies will be carried out to biochemically define these novel species. Cytotoxicity against tumor lines and antiviral activity will be determined.